Solid mammary tumors were formed in nude mice by s.c. injections of a number of human breast cancer cell lines. Tumor formation was estrogen-dependent. After the tumor is established estrogen withdrawal failed to induce tumor regression. Host modification and aromatase inhibitor studies indicated that the lack of tumor regression was not due to tumor paraendocrine activity nor to a persisting host modification following estrogen withdrawal. Tumor regression was obtained by adriamycin treatment or treatment with the antiestrogen, tamoxifen, which competes for estrogen receptor. Tumors were ten times more sensitive to tamoxifen or adriamycin when the tumor host was deprived of estrogen. This was demonstrable in all tumor lines examined and establishes a role for estrogen in influencing the sensitivity of breast carcinoma to adriamycin. Adriamycin was consistently effective in completing with estrogen for estrogen receptor. The specificity of this competition is now being examined.